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Nervous System
NERVOUS SYSTEM · Describe the organisation and subdivisions of the nervous system. ''' Dorsal cavity- '''CNS- Brain and Spinal Cord PNS- 12 prs cranial , 31 prs spinal nerves-communication between CNS and body Sensory division afferent-impulses from receptors to CNS Motor division efferent- impulses from CNS to effectors 1. Somatic- voluntary-skeletal 2. Visceral- involuntary-:impulses from CNS to smooth, cardiac muscle, glands Sympathetic-mobilizes- Parasym- Conserves energy, functions during rest · Describe the microscopic structure of a neuron. ''' '''Neuron-'''nerve cell-Structural units of N.S -highly specialized, conduct messages-electrical impulses -extreme longevity-with nutrition-function for over 100 years -amitotic- when function as communication links-lose ability to divide- cannot be repaired if destroyed. Exceptions- olfactory epithelium, hippocampal memory regions-contain stem cells-produce new neurons throughout life. -high metabolic rate-require continuous glucose, oxygen '''Structural- classified depending on number of processes extending from cell body-multipolar-interneurons ; bipolar- neurons in retina, olfactory mucosa; unipolar- sensory Functional- ''' Sensory-afferent-to CNS; Motor-efferent- from CNS to effectors; interneurons 99% NERVE CELL- '''Cell body, soma containing nucleolus - Protein, membrane making machinery, ribosomes- Rough ER- NISSL bodies - Mitochondria, microtubules and neurofibrils-bundles of intermediate neurofilaments-shape, integrity - Acts as RECEPTIVE area- info from other neurons - Most cell bodies located in CNS, protected by skull and vertebral column o Clusters of cell bodies in CNS- nuclei o Clusters in PNS-'Ganglia' Processes- ''' o Dendrites- receptive, input region- short, branched- enormous surface area for receiving signals o transfers messages towards Cell body- usually are short dictance-Graded potentials o Finer dendrites-have dentritic spines- '''Axons o CONDUCTING region-generates nerve impulses, transmits them along plasma membrane-Axolemma o Varies-from none to one, short or very long o Very long axons-NERVE Fibre o Single axon arises from Hillock- nerve impulses generated –Trigger zone-conducted along axon to axon terminals –Secretory region o Can be undivided or has branchesangles- Collaterals o Axon or collateral branch producing >10 000 Telodendria- ends called-axon terminals, synaptic knobs, boutons o Lacks Nissl and golgi contained in cell body Myelin sheath, Neurilemma o Myelin-whitish,fatty protein lipoid-covers long, large diameter Axon nerve fibres-–always unmyelinated o Protects, electrically insulates, increases speed of transmission. o PNS-myelin sheath formed by Schwann '''cells- wrap axon, do not touch-form-'''Node of Ranvier-1mm apart o Neurilemma-exposed part of plasma membrane o CNS-myelin formed by –oligodendrites-coil ~60 axons o White matter- Dense Myelinated fibres-fiber tracts o Grey matter- cell bodies and unmyelinated fibers · Identify the components of a synapse. ' · '''Distinguish between myelinated and unmyelinated axons. ' · 'Describe the various types of neuroglia and their functions. ' '''CNS'-' outnumber neurons 10 to 1. Half brain mass o Astrocytes- largest, most abundant, star shaped, most abundant, versatile, anchor neurons to capillaries, guide migration of young neurons, control chemical environ around neurons. o Microglia- long thorny processes-monitor health of neurons, Protective by transforming into macrophage to phagocytize microbes and debris- Immune sytem cells denied access to CNS o Ependymal – squamous shaped to columnar,many ciliated- line central cavities of brain and spinal cord, form permeable barrier between CSF and tissue fluid that baths cells. o Oligodentrocytes- line along thicker neuron fibers in CNS and wrap processes tightly around the fibers- Myelin sheaths PNS- ' o Satellite- surround neuron cell bodies, similar function to astrocytes o Schwann- surround and from myelin sheaths around larger nerve fibres, vital to regeneration of damaged peripheral nerve fibres · '''List the steps involved in the generation of an action potential. ' o Resting state-no ions move through voltage gated channels- -70mv o A stimulus at dendrites causes -Depolarization-membrane potential becomes less negative-Na+ flowing into cell down concentration gradient, passes threshold of -40mv. Causes All or Nothing response o Peak reached at +40mv, the electrochemical gradient for Na+ reaches zero o Repolarization-Na+ ions close and become inactive, K+ begins moving out of cell at slower rate down its concentration gradient. Returns membrane to resting state. o Hyperpolarization- K+ continues moving out of cell o Na+/K+ pump restores the ion gradient across the membrane. During ion restoration there is refractory period when membrane does not respond to stimulus. o Generation of action potential is caused by permeability changes in the membrane · 'Describe the sequence of events that occur at the synapse. ' o '''SYNAPSE- mediates info transfer between neurons or neurons and effector. o Two types- § Electrical-less common type, contain connexons-protien channels, gap junctions, connect cytoplasm of connecting neurons specialized for flow of ions, synchronize activity. Uni/bi directional communication, direct § Chemical- specialized for release and transmission of N.T; unidirectional; not a direct transmission Chemical Synapse- : · knoblike axon terminal of presynaptic neuron containing membrane bound-synaptic vesicles with NT · NT receptor region-on dendrite or cell body of postsynaptic neuron · Separated by synaptic cleft · Electrical signal converts to chemical signal 1. AP reaches presynaptic axon terminal, 2. Depolarization opens Na+ and Voltage gated Ca ++ channels- allow Ca++ to enter terminal, set up substructure to guide NT vesicles down to membrane. 3. Vesicles fuse with membrane and discharge NT by exocytosis into synaptic cleft 4. NT diffuses across cleft 5. NT binds receptors in postsynaptic membrane to open channels, results in graded potentials..chemical converted back to electrical 6. NT removed by – degradation by enzymes, diffusion away from synapse, reuptake by -astrocytes, into neighboring cells- stored or destroyed · Describe the role of neurotransmitters in the nervous system. ''' NT- chemicals responsible for signal transmission between individual neurons. Neuron-can manufacture more than one NT. Produced in soma; packaged into synaptic vesicles, sent to axon; o nerve impulse arrives at presynptic axon o terminal stimulates opening of ca++ channels on membrane. o Ca enter, bind NT vesicles, travel to cleft, bind membrane, release NT via exocytosis o NT diffuses across cleft to postsynaptic neuron/target, binds specific receptor-response Classified- : - chemical structure - function · '''Identify and briefly describe the neurotransmitter receptors found in the nervous system. o Channel linked- mediate fast synaptic transmission-Ionotropic receptors-composed of several protein subunits arranged in a rosette around a pore- As NT binds, the protein changes shape-opens channel-ions pass- Responses-immediate, short, simple: excitatory-small cations, o G-Protein-linked receptors- Metabotropic receptors- response- indirect,complex,slow,prolonged; transmembrane protein complexes-Muscarinic Ach, biogenic amines, neuropeptides;Nt binding inactivates receptor [activated G proteins- control prodn- 2nd messengers eg cAMP, cGMP, diacylglycerol, Ca2+ o · List the common agonists and antagonists of the neurotransmitters: acetylcholine, norepinephrine, serotonin, histamine, glutamate, GABA and glycine. ' · '''Discuss the involvement of neurotransmitters in the pathophysiology of neurological and psychiatric disorders, e.g. anxiety disorders, dementia, depression, schizophrenia, Parkinson’s disease and migraine. ' · 'Discuss how the actions of the neurotransmitters in the CNS could be influenced pharmacologically to treat these disorders. ' 'Anxiety disorders-: ' - '''Benzodiazepines- '''facilitate a BD receptor- inhibition GABAergic transmission. - '''TCAs- '''increase functional activity-NE,5HT- block reuptake - '''SSRIs-'''block 5HT reuptake-increase functional activity - '''MAOIs- '''phenelzine-enhance activity of 5HT, NE-inhibit degradation by MAO '''Beta Blockers- '''block beta adrenergic receptors – prevent activity of E/NE - '''Antihistamines-'''block Histamine receptors-prevents functional activity '''Dementia- ALzeimer’s disease-AD- '''medication is available to manage the behavioural symptoms of the disease and treat the symptoms of [[|cognitive]] deterioration-: cognitive- Increase Ach levels-block AChE-Rivastigmine, Donepezil, Galanthamine non cognitive- '''Depression- deficiency of monoamine NT, NE, serotonin; MAOI act as antidepressants by blocking MAOI from breaking down the monamines, allowing presynaptic accumulation. Tricyclics act by blocking membrane transporters which reuptake 5HT or NE- increased extracellular NT conc. 'Schizophrenia- excessive '''imbalance in dopaminergic, glutamatergic systems- overactivity of dopamine; maybe increased dopamine receptors; 5HT- may interact with dopamine. 1st gen antipsychotics-Dopamine antagonists- CPZ, Haloperidol 2nd gen –D & 5HT antagonists- fewer S/E- clozapine, risperidone '''Parkinson’s- '''loss of dopamine and NE producing neurons in Basal nuclei and locus coeruleus. Progressive loss D neurons in Substantia Nigra '''Levodopa-'''prodrug to dopamine-penetrate BBB metabolized/ given with peripheral decarboxylase inhibitor-carbidopa- to reduce peripheral breakdown of D. Also L-DOpa is metabolized by COMT- so COMT inhibitors- '''Migraine- 5HT- serotinagonist- '''stop cranial bv from increasing diameter and getting inflamed- block liberation of 5HT '''NO-' A sterile inflammatory process which involves the liberation of several neuropeptide may increase the diameter of blood vessels and increase the sensitivity of the pain sensing nerve endings around the cranial blood vessels. These mechanisms may be initiated by changes in the concentrations of certain [[|neurotransmitter]], particularly [[|serotonin]] (5-HT), calcitonin [[|gene]]-related [[|peptide]] (CGRP) and nitric oxide (NO) in the brain. · 'Define the terms agonist and antagonist, giving examples of each. ' Agonist –an entity that increases the functional activity as NT binds to the receptor Eg. Pilocarpine-ach agonist Antagonist- an entity which decreases functional activity as NT binds to the receptor preventing normal ligand binding. antagonist-neostigmine · Explain the use of therapeutic agents in modifying neurotransmitter receptor interaction, give an example. There can be several changes in neurotransmission, apart from direct receptor effects. Examples of these are - increased number of impulses- inc NT release-nicotine,marijuana - release of NT with /without impulses-inc NT release- amphetamines - blocked reuptake-more NT in cleft- amphetamine Example- AchE reduces the degradation of Ach in the synaptic cleft resulting in prolonged / increased presence of Ach function. Rivastigmine- used in Alzeimers-mimics Ach